Reduction of chemical noise in a MALDI mass spectrometer by in-trap photodissociation of matrix cluster ions

Abstract

A MALDI mass spectrometer includes a radiation source, such as a gas or solid state laser, that emits a beam of radiation (typically in the UV or IR wavelengths) directed along the central axis of a linear ion trap in which analyte ions and matrix cluster ions are confined. The radiation beam has a wavelength that is strongly absorbed by the matrix cluster ions. The absorption of radiation by the matrix cluster ions produces dissociation of the matrix cluster ion into fragments having mass-to-charge ratios that lie below a mass-to-charge ratio range of interest. Thus, chemical noise associated with matrix cluster ions is reduced or eliminated.

Description

FIELD OF THE INVENTION[0001]The present invention relates generally to mass spectrometers, and more particularly to an apparatus and method for reducing chemical noise arising from the presence of matrix cluster ions in a MALDI mass spectrometer.BACKGROUND OF THE INVENTION[0002]One major problem faced by designers and users of mass spectrometers is the presence of chemical noise in the mass spectra. The source and appearance of chemical noise will vary according to the analyte type, ionization method, and operating conditions. For mass spectrometers utilizing matrix-assisted laser desorption / ionization (MALDI), most of the chemical noise is represented by groups of peaks corresponding to matrix cluster ions with compositions described by (Matrixx−(y+z−1)H)+NayKz(with possible loss of water or ammonia), where x, y, and z may vary from 0 to 8. In addition to these peaks, there is a background noise of complex structure that spans the entire range of mass-to-charge ratios, and which ma...

AI Technical Summary

Benefits of technology

[0004]In brief, a mass spectrometer according to an embodiment of the present invention includes a MALDI source, ion transport optics, a linear ion trap, and a laser or other radiation source configured to direct a radiation beam along a longitudinal axis of the ion trap. Ions produced by the MALDI source, which include both analyte ions and matrix cluster ions, are trapped within the linear trap and are cooled by collisions with damping gas molecules such that the ion cloud (the volume occupied by most of the ions) shape approximates a narrow cylinder, having a typical diameter of less than 1 mm. The radiation beam is positioned to overlap with and preferably envelop the ion cloud. The radiation source may take the form of a pulsed gas or solid-state laser that emits UV or IR light at a frequency that is strongly absorbed by the matrix cluster ions but is less efficiently absorbed by the analyte ions. The absorption of radiation by the matrix cluster ion results in the breaking of at least one bond and the consequent dissociation of the matrix cluster ion into two or more low molecular weight components having mass-to-charge ratios that lie below the mass-to-charge ratio range of interest (the range in which the analyte and / or its fragments lie). Thus, chemical noise associated with matrix cluster ions is reduced or eliminated. In certain implementations of the invention, the photodissociation process may be applied after or during isolation of an ion of interest in the ion trap.

[0005]In accordance with an alternative embodiment, a supplemental oscillating field may be generated in the ion trap to cause analyte ions to travel outside of the region irradiated by the laser beam while still remaining confined within the trap. The frequency (or range of frequencies) of the supplemental field is selected such that the matrix cluster ions are not excited, or excited to a lesser degree relative to the analyte ions, and so the matrix cluster ions stay within the irradiated. In this manner, the analyte ions receive less radiation than the matrix cluster ions. This embodiment may be particularly useful to avoid undesired fragmentation when the analyte ions are absorptive at the laser beam frequency.

Problems solved by technology

One major problem faced by designers and users of mass spectrometers is the presence of chemical noise in the mass spectra.

Chemical noise may be particularly problematic in high-throughput operations where careful and frequent cleaning of the MALDI substrate surface (which eliminates some sources of chemical noise) is not practical.

However, applying heat thermally to the matrix cluster ions may have the undesirable effect of promoting decomposition of labile analyte ions.

Furthermore, heating the analyte ions increases their kinetic energy and may adversely affect transmission and trapping efficiencies.

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